The defective enzyme is ferrochelatase, which is responsible for the insertion of iron into protoporphyrin to form haem (See Introduction to porphyria). Large amounts of protoporphyrin accumulate in erythrocytes (which will fluoresce under ultraviolet light), plasma and in severe cases, in hepatocytes.
The inheritance is complex. The basic trait is transmitted as an autosomal dominant, but the penetrance is incomplete and fewer than 50% of the offspring of affected parents are affected. Occasional patients with erythropoietic protoporphyria develop severe liver disease as a result of the accumulation of large amounts of protoporphyrin within hepatocytes: this form of the porphyria tends to be transmitted as an autosomal recessive trait, suggesting that homozygotes or compound heterozygotes (patients inheriting two mutations on different alleles) are at risk of the liver disease (See Inheritance of porphyria).
Patients develop skin disease only and are not at risk of the acute attack. The skin disease associated with erythropoietic protoporphyria is characteristic, and does not conform to the same pattern of vesiculo-erosive photodermatitis seen in other forms of porphyria (See Skin disease in porphyria). Accumulation of porphyrins in the erythrocytes, plasma and skin leads to an unusual syndrome of immediate photosensitivity, felt by the patient as warmth, burning, stinging and pain in sun-exposed areas. This is sometimes described as solar urticaria. Typically patients have an individual threshold for sun-exposure. They learn that once they have been exposed to sun for more than a certain period of time (usually about 30 minutes) the symptoms will start. Immediately after sun exposure, the skin may be erythematous and oedematous. Patients do not develop the erosions and blisters typical of other forms of porphyria. Eventually chronic changes develop: these are limited to mild coarsening and grooving of the skin over the bridge of the nose and the knuckles (Click on the image).
Occasional patients with erythropoietic protoporphyria develop liver disease, known as protoporphyric hepatopathy. This results from the accumulation of large amounts of protoporphyrin in hepatocytes, which leads to disturbed liver function, cirrhosis and ultimately liver failure. Such patients are candidates for liver transplantation.
Patient should limit their exposure to the sun (See Management of skin disease).
Ingestion of carotenoids such as beta carotene results in the development of a yellowish layer in the skin which effectively filters out the ultraviolet wavelengths of light which aggravate the skin disease, and may additionally protect against damage by functioning as an antioxidant and free radical scavenger. Beta-carotene in sufficiently large doses may ameliorate symptoms and prolong the patient's ability to tolerate sunlight. Commercial preparations do not contain sufficient beta-carotene for this effect. Patients may buy beta-carotene directly from the manufacturers as a powder. The initial dose is 100 mg daily. This may be increased to 150 mg and 200 mg daily if necessary. These large doses are safe and well tolerated. Typically patients develop carotenodermia ( an orange discolouration of the skin) after about 1 month, and thereafter note an improvement in sun tolerance. The related compound canthaxanthine is sometimes combined with the beta-carotene to result in a slightly less artificial skin colour, but carries the risk of crystallisation in the retina.
Patients with abnormal tests of liver function require specialist referral. They should be treated with oral sorbents such as oral activated charcoal in an attempt to reduce the porphyrin load. Patients with liver failure from hepatopathy of candidates for liver transplantation. Note that neither beta-carotene nor charcoal are indicated for any form of porphyria other than erythropoietic protoporphyria.
These are not necessary since patients do not develop acute attacks.